Pulse Oximetry
Pulse oximeter devices based on photoplethysmography techniques are well known in the art. Wikipedia defines pulse oximetry as “a non-invasive method allowing the monitoring of the oxygenation of a patient's hemoglobin.” The subject's skin at a ‘measurement location’ is illuminated with two distinct wavelengths of light and the relative absorbance at each of the wavelengths is determined.
Wikipedia describes usage of pulse oximeter devices as follows:                A sensor is placed on a thin part of the patient's body, usually a fingertip or earlobe, or in the case of a neonate, across a foot, and a light containing both red and infrared wavelengths is passed from one side to the other. Changing absorbance of each of the two wavelengths is measured, allowing determination of the absorbances due to the pulsing arterial blood alone, excluding venous blood, skin, bone, muscle, fat, and (in most cases) fingernail polish. Based upon the ratio of changing absorbance of the red and infrared light caused by the difference in color between oxygen-bound (bright red) and oxygen-unbound (dark red or blue, in severe cases) blood hemoglobin, a measure of oxygenation (the percent of hemoglobin molecules bound with oxygen molecules) can be made.        
FIG. 1 illustrates extinction curves for both hemoglobin and oxihemoglobin. As is evident from FIG. 1, at a wavelength in the visible red spectrum (for example, at 660 nm), the extinction coefficient of hemoglobin exceeds the extinction coefficient of oxihemoglobin. At a wavelength in the near infrared spectrum (for example, at 940 nm), the extinction coefficient of oxihemoglobin exceeds the extinction coefficient of hemoglobin.
“Pulse Oximetry” by Dr. V. Kamat Indian J. Anesth. 2002; 46(4), 261-268 Kamat provides an overview of known features of Pulse Oximetry. The Kamat document describes various features of Pulse Oximetry as follows:
“The pulse oximeter combines the two technologies of spectrophotometry (which measures hemoglobin oxygen saturation) and optical plethysmography (which measures pulsatile changes in arterial blood volume at the sensor site).
Detection of oxygen saturation of hemoglobin by spectrophotometry is based on Beer-Lambert law, which relates the concentration of a solute to the intensity of light transmitted through a solution. In order to estimate the concentration of a light absorbing substance in a clear solution from the intensity of light transmitted through the solution, one needs to know the intensity and wavelength of incident light, the transmission path length, and absorbance of the substance at a specific wavelength (the extinction coefficient).
Modern pulse oximeters consist of a peripheral probe together with a microprocessor unit displaying a waveform, the oxygen saturation and the pulse rate. The probe is placed on the digit, earlobe or nose. Within the probe are two LEDs, one in the visible red spectrum (660 nm) and the other in the infrared spectrum (940 nm). The beams of light pass through the tissues to the photo detector. During passage through the tissues some light is absorbed by blood and soft tissues depending on the concentration of hemoglobin. The amount of light absorption at each frequency depends upon the degree of oxygenation of hemoglobin within the tissues.
There are several technical problems in accurately estimating oxygen saturation by this method, as scatter, reflection and absorbance of light by other tissue and blood components could confound the values. The system needs to isolate absorbance of arterial blood from venous blood, connective tissue and other extraneous matter. This can be accomplished easily as arterial blood is pulsatile unlike other tissue. Thus the pulse added signal can be distinguished from nonpulsatile signal by filtering the extraneous noise.
The microprocessor can select out the absorbance of the pulsatile fraction of the blood i.e. that due to arterial blood (AC), from the constant absorbance by nonpulsatile venous or capillary blood and other tissue pigments (DC), thus eliminating the effect of tissue absorbance to measure the oxygen saturation of arterial blood.
The pulsatile expansion of the arteriolar bed produces an increase in path length thereby increasing the absorbance. All pulse oximeters assume that the only pulsatile absorbance between the light source and the photodetector is that of arterial blood. The microprocessor first determines the AC component of absorbance at each wavelength and divides this by the corresponding DC component. From the proportions of light absorbed by each component at the two frequencies it then calculates the ratio (R) of the “pulse-added” absorbance.
  R  =                    AC        660            /              DC        660                            AC        940            /              DC        940            
The AC fluctuation is due to the pulsatile expansion of the arteriolar bed due to the volume increase in arterial blood in the vasculature. In most conventional pulse oximeters, in order to measure the AC fluctuation, measurements are taken at different times including a first measurement time at or near a ‘peak’ and at a second measurement time at or near a ‘valley’ (see FIG. 2). The ‘peak’ and ‘valley’ measurements are compared in order to compute the aforementioned R parameter (often referred to as y in the literature).
Because difference in measured light absorption at the two times is due primarily to the fact that the light needs to traverse a different volume of blood at the two measurement times, the measurement provided by pulse oximeters is said to be a ‘volumetric measurement’ descriptive of the differential volumes of blood present at a certain location within the patient's arteriolar bed at different times.
In pulse oximetry, the light absorbance values measured at different times are compared—for example, by comparing (e.g. by computing some sort of difference function to determine the relative magnitudes of the AC and DC components) a first measurement acquired at one of the (i is a positive integer) ‘peak times’ tipeak with a measurement acquired at one of the measurement acquired at one of the ‘valley times’ tivalley. Because the human pulse is typically on the order of magnitude of one 1 HZ, typically the time differences between these ‘pairs of time’ (i.e. one peak, one valley) are on the order of magnitude of milliseconds or tens of milliseconds or hundreds of milliseconds. Thus, in most conventional oximeters, light absorbance measurements are acquired at a frequency of around 10-100 of Hz.
Dynamic Light Scattering
Dynamic light scattering is a tool for measuring a variety of blood parameters.
Dynamic light scattering (DLS) is a well-established technique to provide data on the size and shape of particles from temporal speckle analysis. When a coherent light beam (laser beam, for example) is incident on a scattering (rough) surface, a time-dependent fluctuation in the scattering properties of the surface and thus in the intensity of the light scattering (transmission and/or reflection) from the surface is observed. These fluctuations are due to the fact that the particles are undergoing Brownian or regular flow motion and, so, the distance between the particles is randomly changing with time. This scattered light then undergoes either constructive or destructive interference with the light scattered by surrounding particles that results in the random intensity fluctuations. Within these intensity fluctuations information about the time scale of particles movement is contained. The scattered light forms the speckle pattern, being detected in the far diffraction zone. The laser speckle is a random interference pattern produced at the screen or photodetector plane by the coherent light reflected or scattered from different spots on the illuminated surface. If the scattering particles are moving, a time-varying speckle pattern is generated. The intensity variations of this pattern contain information about the scattering particles. The detected signal is amplified and digitized for further analysis by using the autocorrelation function (ACF) technique. The technique is realized either by heterodyne or by a homodyne DLS setup.
As discussed in WO 2008/053474, incorporated herein by reference in its entirety, DLS may be used to probe blood parameters during occlusion (see FIG. 5 of WO 2008/053474 and the accompanying discussion) such that it is possible to derive viscosity and ‘scatterer size’ (in this case, average size of red blood cell aggregates or Rouleaux).
DLS techniques are not limited to measurements of post-occlusion signals. DLS techniques are also useful for determining a local pulse rate of the subject at the ‘measurement site’ illuminated by the coherent light according to the local optical properties of the measurement sight. The skilled artisan is referred, for example, to FIG. 9 of WO 2008/053474 and the accompanying discussion.
In contrast to photoplethysmography which is used to measure time-dependent volumetric properties of blood from light intensity measurements descriptive of a transmission optical path length between a light source and a photodetector, DLS techniques are employed to measure time-dependent velocities of scatterers (i.e. red-blood cells or aggregates thereof) suspended within the plasma. In one example, it is possible to analyze rapid fluctuations of the light response signal to determine Brownian velocities of particles during occlusion (see FIG. 5 of WO 2008/053474 and the accompanying discussion). In another example, it is possible to determine a blood velocity changes profile within a blood vessel for the laminar flow of suspended scatterers (i.e. red-blood cells or aggregates thereof). From the flow profile a magnitude of shear forces within the blood vessels can be easily determined.
Both PPG and DLS techniques may be employed to derive blood dynamic parameters from the dynamic response of living tissue to light. However, speckle analysis should entail acquiring measurement data values at a much greater frequency (and comparing/computing functions of these measurement data values) than is needed for photoplethysmography—for example, a frequency of at least 3 kHZ or at least 5 kHZ or at least 10 kHZ. For example, in many implementations, measurement values having ‘time gaps’ of less than one half of a millisecond are compared to compute the velocity of a scatterer.
One salient feature provided by some embodiments of DLS is the ability to compute a blood rheological parameter according to ‘very short time scale trends’ (i.e. as opposed to only average values). Thus, one or more DLS measurements may be carried out in accordance with a difference of measurement values that are separated, in time, by less than one millisecond or less than 0.5 millisecond. This is because DLS may measure ‘rapidly-fluctuate physical phenomena’ which fluctuate on a sub-millisecond time scale. Conventional PPG devices operate (for example, to derive concentration parameters) by quantifying data trends over a time scale of around 10 milliseconds.
In one example, autocorrelation techniques are used. In another example, power spectrum techniques are used. In yet another example, it is possible to compute standard deviations of the ‘frequent measurements’ where consecutive measurements have time gaps of less than 0.5 milliseconds. These statistical functions (or any other statistical function) may be computed for at least 100 measurements that occur within a period of time that is at most 40 milliseconds or for at least 250 measurements that occur within a period of time that is at most 100 milliseconds or for at least 500 measurements that take place within a time period that is at most 200 milliseconds.
As shown in FIG. 3, there are two types of dynamic light scattering measurements. The example on the left hand side of FIG. 3 relates to ‘single scattering’ whereby photons emitted by the coherent light source 104 collide only once (and are hence redirected) with one of the scatterers (typically a RBC or an aggregate thereof) before being re-directed by the scatterer and reaching photodetector 108. In the example on the right hand side of FIG. 3, the photons are subjected to multiple collisions with scatterers before reaching the photodetector. In the example of FIG. 3, for the ‘single scattering case’ the offset distance d1 between light source 104 photodetector 108 is relatively small—for example, less than 4 mm or less than 3 mm or less than 2.5 mm. For the ‘multiple scattering case’ the offset distance d2 between light source 104 photodetector 108 may be larger—for example, at least 6 mm or around 10 mm.
The aforementioned examples where DLS is used to detect pulse rate, plasma viscosity or RBC aggregate size may relate primarily to the ‘single scatter’ case where a DLS measurement based primarily on single-scatter events is carried out. In addition, WO 2008/053474 discussed a ‘multiple scatter’ application (with reference to FIG. 18 of WO 2008/053474 and to the accompanying discussion on page 20) where a DLS measurement of oxygen saturation based primarily on multiple-scatter events is carried out. This specific example relates to ‘multi-wavelength’ DLS.
The following patent documents and non-patent publications describe potentially relevant background art, and are each incorporated herein by reference in their entirety: WO 2008/053474, U.S. Pat. Nos. 4,928,692, 4,960,126, 6,793,256, 6,763,256; 5,598,841, 6,553,242, 7,336,982 and 7,018,338.